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Article

Renal Cell Carcinoma: A Study through NMR-Based Metabolomics Combined with Transcriptomics

by
Rosa Ragone
1,†,
Fabio Sallustio
1,2,3,†,
Sara Piccinonna
1,
Monica Rutigliano
2,
Galleggiante Vanessa
2,
Silvano Palazzo
2,
Giuseppe Lucarelli
2,
Pasquale Ditonno
2,
Michele Battaglia
2,
Francesco Paolo Fanizzi
1,3 and
Francesco Paolo Schena
1,2,3,*
1
Consorzio C.A.R.S.O., Centro di Addestramento e Ricerca Scientifica in Oncologia, Strada Provinciale Casamassima Km 3, Valenzano (Bari) 70010, Italy
2
Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
3
Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Prov.le Lecce-Monteroni, Lecce 73100, Italy
*
Author to whom correspondence should be addressed.
†
These authors have contributed equally to this work.
Diseases 2016, 4(1), 7; https://doi.org/10.3390/diseases4010007
Submission received: 25 September 2015 / Revised: 15 December 2015 / Accepted: 15 January 2016 / Published: 22 January 2016
(This article belongs to the Special Issue Advances and Applications of Metabolomics in Human Diseases)
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Abstract

Renal cell carcinoma (RCC) is a heterogeneous cancer often showing late symptoms. Until now, some candidate protein markers have been proposed for its diagnosis. Metabolomics approaches have been applied, predominantly using Mass Spectrometry (MS), while Nuclear Magnetic Resonance (NMR)-based studies remain limited. There is no study about RCC integrating NMR-based metabolomics with transcriptomics. In this work, 1H-NMR spectroscopy combined with multivariate statistics was applied on urine samples, collected from 40 patients with clear cell RCC (ccRCC) before nephrectomy and 29 healthy controls; nine out of 40 patients also provided samples one-month after nephrectomy. We observed increases of creatine, alanine, lactate and pyruvate, and decreases of hippurate, citrate, and betaine in all ccRCC patients. A network analysis connected most of these metabolites with glomerular injury, renal inflammation and renal necrosis/cell death. Interestingly, intersecting metabolites with transcriptomic data from CD133+/CD24+ tumoral renal stem cells isolated from ccRCC patients, we found that both genes and metabolites differentially regulated in ccRCC patients belonged to HIF-α signaling, methionine and choline degradation, and acetyl-CoA biosynthesis. Moreover, when comparing urinary metabolome of ccRCC patients after nephrectomy, some processes, such as the glomerular injury, renal hypertrophy, renal necrosis/cell death and renal proliferation, were no more represented.
Keywords: RCC; NMR-based metabolomics; urine; transcriptomics; tumoral renal stem cells RCC; NMR-based metabolomics; urine; transcriptomics; tumoral renal stem cells

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MDPI and ACS Style

Ragone, R.; Sallustio, F.; Piccinonna, S.; Rutigliano, M.; Vanessa, G.; Palazzo, S.; Lucarelli, G.; Ditonno, P.; Battaglia, M.; Fanizzi, F.P.; et al. Renal Cell Carcinoma: A Study through NMR-Based Metabolomics Combined with Transcriptomics. Diseases 2016, 4, 7. https://doi.org/10.3390/diseases4010007

AMA Style

Ragone R, Sallustio F, Piccinonna S, Rutigliano M, Vanessa G, Palazzo S, Lucarelli G, Ditonno P, Battaglia M, Fanizzi FP, et al. Renal Cell Carcinoma: A Study through NMR-Based Metabolomics Combined with Transcriptomics. Diseases. 2016; 4(1):7. https://doi.org/10.3390/diseases4010007

Chicago/Turabian Style

Ragone, Rosa, Fabio Sallustio, Sara Piccinonna, Monica Rutigliano, Galleggiante Vanessa, Silvano Palazzo, Giuseppe Lucarelli, Pasquale Ditonno, Michele Battaglia, Francesco Paolo Fanizzi, and et al. 2016. "Renal Cell Carcinoma: A Study through NMR-Based Metabolomics Combined with Transcriptomics" Diseases 4, no. 1: 7. https://doi.org/10.3390/diseases4010007

APA Style

Ragone, R., Sallustio, F., Piccinonna, S., Rutigliano, M., Vanessa, G., Palazzo, S., Lucarelli, G., Ditonno, P., Battaglia, M., Fanizzi, F. P., & Schena, F. P. (2016). Renal Cell Carcinoma: A Study through NMR-Based Metabolomics Combined with Transcriptomics. Diseases, 4(1), 7. https://doi.org/10.3390/diseases4010007

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